A competing renewal Program Project grant designed to integrate recombinant DNA technology, physical chemistry and developmental biology to investigate tissue-specific extracellular matrix (ECM) biomineralization. Our strategy is to identify and characterize specific regions of ECM proteins implicated with biomineralization and to examine their function(s) during the formation of the dentine-enamel junction. Our research program represents ten investigators who propose four interdisciplinary subprogram projects and an administrative core designed to investigate cell- and ECM-mediated biomineralization. Using the developing mouse molar tooth organ, these four projects pursue a central hypothesis that odontogenic cells and their ECM, produced as a function of time and position within the tooth organ, regulate tissue-specific biomineralization. Specifically, unique regions within protein structure (e.g. amelogenin, a putative amelogeninase, dentine phosphoprotein) including post-translational modification (e.g. kinase-directed phosphorylation of dentine phosphoprotein), control intra- and intermolecular interactions required for calcium hydroxyapatite crystallite (HAP) formation and patterns of crystal growth. this current proposal represents a competitive renewal application following 21 years of previous funding. All of the participants from the last five years of support remain in this proposal with the addition of several new investigators. The range of expertise ranges from cellular and molecular biology (e.g. cell culture, organ culture, gene cloning and sequencing, site-directed mutagenesis, polymerase chain reaction) to the principles of physical chemistry (e.g. x-ray crystallography, computer-assisted molecular modeling, electron diffraction analysis) as they relate to molecular interactions regarding biomineralization.